Recruitment of leukocytes from blood into cutaneous inflammatory sites occurs via a stepwise cascade of adhesion events. T cell trafficking to sites of cutaneous inflammation has been closely associated with expression of the cutaneous lymphocyte antigen (CLA), a carbohydrate epitope that serves as an E-selectin ligand on T cells and mediates the first, crucial steps in T cell recruitment. CLA has been shown previously to be differentially expressed on a leukocyte sialomucin called P-selectin glycoprotein ligand-1 (PSGL-1). We have recently discovered that CD43, a sialomucin similar in structure to PSGL-1, and an unidentified 100 kD sialoglycoprotein (gpl00) can also serve as E-selectin ligands on CLA+ T cells. These previously unknown T cell selectin ligands were identified using two novel assay methods we have developed. There is, at present, no published data regarding the structure or regulation of E-selectin ligand determinants on CD43 or a 100 kD glycoprotein on T cells. These previously unknown ligands may play important, currently undefined roles in immune surveillance and the recruitment of leukocytes to inflammatory loci. In this proposal, we outline experiments that will characterize the individual E-selectin ligands expressed on T cells. The identification of common motifs among these ligands could lead directly to the design and development of common inhibitors of E-selectin mediated adhesion that may be of significant value in inflammatory disorders such as chronic autoimmune disease, graft-versus-host disease and transplantation rejection.

R01AI056084

2003-09-15

2008-12-31